Immune checkpoint therapies targeting the programmed cell death protein 1 (PD-1) axis have resulted in groundbreaking improvements in clinical response in multiple human cancers (Brahmer et al., N Engl J Med 2012, 366: 2455-65: Garon et al. N Engl J Med 2015, 372: 2018-28: Hamid et al., N Engl J Med 2013, 369: 134-44; Robert et al., Lancet 2014, 384: 1109-17: Robert et al., N Engl J Med 2015, 372: 2521-32; Robert et al., N Engl J Med 2015, 372: 320-30; Topalian et al., N Engl J Med 2012, 366: 2443-54; Topalian et al., J Clin Oncol 2014, 32: 1020-30; Wolchok et al., N Engl J Med 2013, 369: 122-33). The interaction of the PD-1 receptor on T-cells with its ligands, PD-L1 and PD-L2, on tumor and immune infiltrating cells regulates T-cell mediated immune responses and may play a role in immune escape by human tumors (Pardoll D M. Nat Rev Cancer 2012, 12: 252-64). Binding of PD-1 to either of its ligands results in delivery of an inhibitory stimulus to the T cell. Immune therapies targeting the PD-1 axis include monoclonal antibodies directed to the PD-1 receptor (OPDIVO (nivolumab), Bristol-Myers Squibb, Princeton, N.J. and KEYTRUDA (pembrolizumab), Merck and Co., Inc. Kenilworth, N.J.) and also those that bind to the PD-L1 ligand (MPDL3280A; TECENTRIQ (atezolizumab), Genentech, San Francisco, Calif.). Both therapeutic approaches have demonstrated anti-tumor effects in several cancer types.
PD-L2 protein expression has been detected in the tumor microenvironment and on antigen presenting cells under certain conditions. Also, northern blot analysis of various tissues indicates that PD-L2 RNA is expressed in heart, placenta, liver, pancreas, spleen, lymph node, lung, smooth muscle and thymus. Thus, the ability to detect PD-L2 protein in situ in human tissues (e.g., by IHC assay) is important for investigating the biological activity of PD-L2, as well as for evaluating the anti-tumor efficacy of drugs targeting the PD-1 axis.
IHC assay is one of the most common techniques to detect a protein of interest in human tissue samples. Tumor tissue samples removed from a human patient are typically preserved for subsequent analysis by freezing individual tissue sections or by preparing formalin-fixed paraffin-embedded (FFPE) tissue sections. A need exists for anti-human PD-L2 antibodies that are capable of producing staining patterns for both frozen and FFPE tissue sections that have similar specificity and sensitivity, and to do so in a reproducible manner.